Non-sedating dexmedetomidine treatment regimens

Abstract

Disclosed herein are methods of administering relatively high doses of dexmedetomidine or a pharmaceutically acceptable salt thereof to a human subject, without also inducing significant sedation. The disclosed methods are particularly suitable for the treatment of agitation, especially when associated with neurodegenerative and/or neuropsychiatric diseases such as schizophrenia, bipolar illness such as bipolar disorder or mania, dementia, depression, or delirium.

The invention claimed is: 
     
       1. A method of treating agitation associated with schizophrenia or bipolar disorder in an agitated human subject, comprising:
 administering a composition comprising a sole active agent to the oromucosal of the agitated human subject, wherein the active agent consists of dexmedetomidine or a pharmaceutically acceptable salt thereof; 
 wherein the human subject has a corrected QT interval using Fridericia's correction method (QTcF) of less than 470 msec; and 
 wherein the subject is administered a first dose of dexmedetomidine or a pharmaceutically acceptable salt thereof, about 120 micrograms to about 180 micrograms. 
 
     
     
       2. The method of  claim 1 , wherein the first dose of dexmedetomidine is about 120 micrograms of dexmedetomidine or a pharmaceutically acceptable salt thereof. 
     
     
       3. The method of  claim 2 , wherein the treatment comprises a decrease in the agitation that is statistically significant at about 30 minutes following the administration. 
     
     
       4. The method of  claim 1 , wherein the first dose of dexmedetomidine is about 180 micrograms of dexmedetomidine or a pharmaceutically acceptable salt thereof. 
     
     
       5. The method of  claim 4 , wherein the treatment comprises a decrease in the agitation that is statistically significant at about 20 minutes following the administration. 
     
     
       6. The method of  claim 1 , wherein the composition is in the form of a film. 
     
     
       7. The method of  claim 6 , wherein the dexmedetomidine or a pharmaceutically acceptable salt thereof is administered sublingually. 
     
     
       8. The method of  claim 6 , wherein the dexmedetomidine or a pharmaceutically acceptable salt thereof is administered buccally. 
     
     
       9. The method of  claim 1 , wherein the first dose of dexmedetomidine is about 120 micrograms of dexmedetomidine or a pharmaceutically acceptable salt thereof, wherein the dexmedetomidine or a pharmaceutically acceptable salt thereof is in the form of a sublingual film, and wherein treatment comprises a decrease in the agitation that is statistically significant at about 30 minutes following the administration. 
     
     
       10. The method of  claim 9 , wherein the subject does not have an advanced heart block. 
     
     
       11. The method of  claim 9 , wherein the subject has a QTcF of less than 450 msec and wherein the subject does not have an advanced heart block. 
     
     
       12. The method of  claim 1 , wherein the first dose of dexmedetomidine is about 180 micrograms of dexmedetomidine or a pharmaceutically acceptable salt thereof, wherein the dexmedetomidine or a pharmaceutically acceptable salt thereof is in the form of a sublingual film, and wherein treatment comprises a decrease in the agitation that is statistically significant at about 20 minutes following the administration. 
     
     
       13. The method of  claim 12 , wherein the subject does not have an advanced heart block. 
     
     
       14. The method of  claim 1 , wherein the subject has a QTcF of less than 450 msec. 
     
     
       15. The method of  claim 1 , wherein the subject does not have an advanced heart block. 
     
     
       16. The method of  claim 12 , wherein the subject has a QTcF of less than 450 msec and wherein the subject does not have an advanced heart block. 
     
     
       17. The method of  claim 1 , further comprising administering a second dose of dexmedetomidine or pharmaceutically acceptable salt thereof of about 60 micrograms to about 90 micrograms to the human subject about 0.5 hours to about 12 hours after administration of the first dose. 
     
     
       18. The method of  claim 17 , wherein the second dose of dexmedetomidine or pharmaceutically acceptable salt thereof is about 60 micrograms. 
     
     
       19. The method of  claim 17 , wherein the second dose of dexmedetomidine or pharmaceutically acceptable salt thereof is about 90 micrograms. 
     
     
       20. The method of  claim 17 , wherein the second dose of dexmedetomidine or pharmaceutically acceptable salt thereof is administered about 2 hours after administration of the first dose. 
     
     
       21. The method of  claim 17 , wherein the second dose of dexmedetomidine or pharmaceutically acceptable salt thereof is administered about 4 hours after administration of the first dose. 
     
     
       22. The method of  claim 17 , wherein the second dose of dexmedetomidine or pharmaceutically acceptable salt thereof is administered about 6 hours after administration of the first dose. 
     
     
       23. The method of  claim 17 , wherein the second dose of dexmedetomidine or pharmaceutically acceptable salt thereof is administered about 8 hours after administration of the first dose. 
     
     
       24. The method of  claim 17 , wherein the second dose of dexmedetomidine or pharmaceutically acceptable salt thereof is administered about 10 hours after administration of the first dose. 
     
     
       25. The method of  claim 17 , wherein the second dose of dexmedetomidine or pharmaceutically acceptable salt thereof is administered about 12 hours after administration of the first dose.